Collection, processing and purification of biological samples are important processes in a range of medical therapies and procedures. Important biological samples used as therapeutic and/or re-infusion agents include whole blood and purified blood components, such as red blood cells, platelets, white blood cells and plasma. In the field of transfusion medicine, one or more whole blood components are directly introduced into a patient's blood stream to replace a depleted or deficient component. Infusion of plasma-derived materials, such as blood proteins, also plays a critical role in a number of re-infusion processes and other important therapies. For example, plasma-derived immunoglobulin is commonly provided to supplement a patient's compromised immune system. Due to increases in the demand for purified biological samples for transfusion, infusion and transplantation therapies, substantial research efforts have been directed at improving the availability, safety and purity of biological samples used as therapeutic and/or re-infusion agents.
While biological samples used for re-infusion or other purposes are currently safer than in the past, the risk of exposure to pathogens in human blood samples remains significant. A large number of deleterious contaminants have been identified in intracellular and extracellular fractions of human blood. For example, it is estimated that approximately 1 in 34,000 donated blood and blood component samples are contaminated with viral contaminants such as human immunodeficiency virus type I/II (HIV), hepatitis B and C (HVB and HVC) or human T-lymphotropic virus type I/II (HTLV I/II). Bacterial contaminants are even more common than viral contaminants in donated blood and blood component samples and may reach an incidence of contamination as high as about 1 in 2000 samples. Contamination of donated blood components with donor leukocytes is another frequently encountered problem.
In addition to these known risks, it has also been demonstrated that human blood reservoirs are routinely contaminated with other pathogens which are not assayed in conventional blood screening protocols, including transfusion-transmitted virus, hepatitis G virus, human herpes virus 8, HTLV-2, hepatitis A, TT virus, SEN-V malaria, babesia, trypanosome, and parvo B19 virus.
Over the last decade, a number of methods have been developed for reducing the risks associated with pathogenic contaminants in biological samples, especially donated blood components. One promising approach to reducing risks associated with contamination of these materials is to use chemical or physical pathways to reduce the biological activities of pathogens present in biological samples or render them incapable of replication. Over the last decade, a variety of methods for reducing the biological activities of pathogens in biological fluids have been developed, including, direct photoreduction, use of detergents for inactivating viruses having lipid membranes, chemical treatment methods and photoinduced chemical reduction techniques. Due to their compatibility with high-volume pathogen inactivation, efficiency and demonstrated efficacy, photoinduced chemical reduction and direct photoreduction have emerged as two especially promising techniques for treating biological samples. U.S. Pat. Nos. 6,277,337, 5,607,924, 5,545,516, 4,915,683, 5,516,629, and 5,587,490 describe exemplary applications of photoinduced chemical reduction methods and direct photoreduction methods for reducing of pathogens in blood.
In photoinduced chemical reduction methods, effective amounts of one or more photosensitizers are added to a biological fluid, which may be subsequently mixed and illuminated with electromagnetic radiation. Illumination activates the photosensitizers, thereby initiating chemical reactions and/or physical processes which kill the pathogens present in the sample or substantially prevent pathogens from replicating. In direct photoreduction methods, illumination with electromagnetic radiation having selected wavelengths directly results in pathogen reduction.
An important consideration in photoinduced chemical reduction and direct photoreduction methods is that exposure of some blood components to electromagnetic radiation can deleteriously affect their biological activities and vitalities. Decreases in biological activities and vitalities from exposure to electromagnetic radiation may reduce the effectiveness of these materials as therapeutic and/or re-infusion agents. Therefore, a compromise often exists in photoinduced chemical reduction and direct photoreduction methods between optimizing the extent of pathogen reduction and minimizing damage to blood components comprising therapeutic and/or re-infusion agents.
Another important consideration in photoinduced chemical reduction and direct photoreduction methods is the ability of these methods to provide uniform treatment for fluid samples having characteristics that are commonly subject to variation, such as the volumes, masses, donor identities and the concentrations of cellular and non-cellular components of samples. For example, conventional pathogen reduction procedures that deliver the same net radiant energy per illuminated area to all treated blood and blood component samples may result in nonuniform treatment that varies systematically with the volume of the blood or blood product samples undergoing treatment. As blood and blood components typically exhibit a range of sample volumes depending on the physical attributes of the donor and the procedures employed for collection and processing, this practical limitation may result in blood products having pathogen concentrations and therapeutic qualities that vary significantly. Such undesirable variations can significantly undermine quality control efforts and may negatively impact product validation and regulatory approval.
It will be appreciated from the foregoing that a clear need exists for methods and devices for uniformly treating biological fluids with electromagnetic radiation. Specifically, methods and devices are needed that provide equivalent treatment of fluid samples with electromagnetic radiation, regardless of properties of the samples subject to variation such as the volumes or masses of the samples. In addition, methods and devices for treating fluid samples with electromagnetic radiation are needed that generate treated samples having comparable levels of pathogens and having components comprising therapeutic and/or re-infusion agents exhibiting comparable biological activities and viabilities.